Dopaminergic transmission in the brain's mesocorticolimbic system is thought to be a significant factor in alcohol abuse and dependence. Most research on the dopaminergic response to alcohol and its conditioned cues is nevertheless done in rodents. The extent to which these rodent models translate to human alcohol use disorders is unknown. Therefore the long term goal of our proposed work is the development of an in vivo human biomarker of striatal dopaminergic responses that can be applied to the study alcoholism and its antecedent risks. We will do this using both positron emission tomography (PET) and the dopamine D2 ligand [11C]raclopride, as well as fMRI. Behavioral paradigms will be employed to study how alcohol's cues relate to dopamine function and cortical activation in subjects with alcoholism. PUBLIC HEALTH RELEVANCE: This research will use a technology called positron emission tomography to study the neurochemical dopamine in the human brain. It will also use a second neuroimaging technique called functional magnetic resonance imaging to examine brain areas that become active in response to certain stimuli. Alterations in the dopamine system, and in the brain's frontal areas, are thought to be highly important to alcoholism, as well as to other addictions. Research such as this has the potential to show how dopamine neurotransmission is altered in alcoholism, and how these alterations relate to brain function in frontal cortex. A better understanding of these phenomena may lead to better diagnosis and treatment.